Triple-Negative Breast Cancer Update

by Lisa A. Carey, MD

Breast cancer is not one disease; it
is a family of diseases that differ from
one another in biology and in their
behavior. While scientists have an increasing
array of tools to identify subtypes
of breast cancer at the molecular level,
doctors rely on three tools to help make
treatment decisions: 1) measurement
of the estrogen receptor (ER), 2) the
related protein progesterone receptor
(PR), and 3) a separate protein, HER2.

These three proteins are important
because they help us identify the different
types of breast cancer, and because
they are drug targets that we use to
determine what kind of treatment is
appropriate for each person.

About 80 percent of breast cancers
are positive for ER and PR. This signals
that the cancer is sensitive to hormones.
For these people, anti-estrogen pills,
like tamoxifen or aromatase inhibitors,
are the keys to treating the cancer or
preventing its recurrence.

Excess HER2 expression (or the
genetic abnormality responsible for this
excess) is found in about 20 percent of
tumors. It means that a cancer may be
sensitive to drugs designed to attack
HER2, like trastuzumab (Herceptin®).

For the 15 percent of breast cancers that are triple negative,
chemotherapy is the mainstay of treatment and the primary
means of keeping these tumors from recurring.

When none of these three proteins is
present, the tumor is called triple negative.
For the 15 percent of breast cancers
that are triple negative, chemotherapy
is the mainstay of treatment and the
primary means of keeping these tumors
from recurring.

There are several myths about triple
negative breast cancer. Myth number
one is that these tumors are destined to
recur. While triple-negative breast cancer
generally has a poorer prognosis
than most other kinds of breast cancer,
the majority of these cancers do not
recur if they are treated effectively with
surgery (with or without radiation) and
chemotherapy.

The second common myth is that
triple-negative breast cancer only affects
African-American women. Several
studies, the most famous of which was
the Carolina Breast Cancer Study,
have consistently shown that the triple-negative
subtype is more common in
black women (and young women). However,
the truth is that any woman can
develop triple-negative breast cancer
and that most African-American women
who are diagnosed have other types
of breast cancer. Part of the Carolina
Breast Cancer Study suggests that risk
factors may be different for triple-negative
breast cancer than for other
more common breast cancers. While
this still needs to be confirmed, there
is early evidence that breast-feeding
and weight control may be effective
in preventing this disease.

Dr. Larry Norton

“The great revolution in the management of
infections happened when medical scientists
knew enough
about these diseases
to shift
their attention
from the organ
involved – lung
for pneumonia,
kidney for pyelonephritis,
etc. –
to the bacteria
actually causing
the illness:
streptococcus,
staphylococcus, and so on. A similar revolution
is now happening in cancer medicine; we are
learning to focus less on the organ from which
the tumor originates and more on the abnormalities
in DNA, RNA, and other molecules that
make the cancer behave as it does.

“In her article addressing triple-negative
breast cancer, Dr. Lisa Carey – one of the
world leaders in breast cancer research –
describes the biology of these diseases, outlining
exciting developments aimed toward
prevention, as well as treatment. She also
sets the record straight about some common
myths, illustrating how scientific study can
dispel misconceptions and point the way to
a better future.” – Larry Norton, MD, Deputy
Physician-in-Chief for Breast Cancer Programs
at Memorial Sloan-Kettering Cancer Center
in New York, NY.

Myth number three is that triple-negative
breast cancer does not respond
to standard treatments. In fact, the triple-negative
subtype is quite sensitive to
chemotherapy, and advances in chemotherapy
have benefited women with
this disease.

We would love to find a targeted
therapy for triple-negative breast cancer,
but at this point, we do not yet have
treatments beyond chemotherapy for this
disease. The most recent excitement surrounded
a group of drugs called PARP
inhibitors. Sadly, despite early enthusiasm
and evidence that these drugs work
in women with familial breast cancer (the
kind that women who inherit mutations in
the genes BRCA1 or BRCA2 get), it does
not look like they will be effective in
the majority of triple-negative cases.

At the same time, many other drugs
targeting various abnormalities in how
triple-negative cancer cells grow or survive
are in clinical trials, and women
should ask their oncologist about trials
available near them to help improve
treatment for women in the future.

What we all hope for the future is
a better understanding of the causes of
all subtypes of breast cancer, thanks to
today’s ongoing studies. We also want to
be able to give lifestyle and healthy
behavior recommendations for breast
cancer prevention
that are
backed by scientific
evidence.
We count on
developing more
effective treatments,
including
realizing the
promise of targeted
therapy for
triple-negative
breast cancer, so that chemotherapy for
breast cancer becomes a distant memory.

♦ ♦ ♦ ♦ ♦

Dr. Lisa Carey is the Preyer Distinguished
Professor of Breast Cancer Research at the
University of North Carolina School of
Medicine and associate director of Clinical
Research at UNC Lineberger Comprehensive
Cancer Center in Chapel Hill, NC.

This article was originally published in Coping® with Cancer magazine,
September/October
2012.